Analysis and modeling of the variable region of camelid single-domain antibodies

Journal of Immunology

Volumn 186, Issue 11, 2011, Pages 6357-6367

  Sircar, Aroop ^a,d   Sanni, Kayode A ^b   Shi, Jiye ^c   Gray, Jeffrey J ^a  

^a Johns Hopkins University   (United States)

^b University of Marylandw Baltimore County   (United States)

^c UCB PHARMA   (Belgium)

^d EMD Serono Research Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY;

AMINO ACID SEQUENCE; ARTICLE; ARTIODACTYLA; CONTROLLED STUDY; DISULFIDE BOND; MOLECULAR MODEL; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN MOTIF; SEQUENCE ALIGNMENT; SEQUENCE HOMOLOGY;

AMINO ACID SEQUENCE; ANIMALS; BINDING SITES, ANTIBODY; CAMELIDS, NEW WORLD; CAMELS; COMPLEMENTARITY DETERMINING REGIONS; DISULFIDES; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN VARIABLE REGION; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; SEQUENCE HOMOLOGY, AMINO ACID;

EID: 79958056394     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1100116     Document Type: Article

References (66)

1. Hamers-Casterman, C., T. Atarhouch, S. Muyldermans, G. Robinson, C. Hamers, E. B. Songa, N. Bendahman, and R. Hamers. 1993. Naturally occurring antibodies devoid of light chains. Nature 363: 446-448. (Pubitemid 23179389)
2. Muyldermans, S., T. N. Baral, V. C. Retamozzo, P. De Baetselier, E. De Genst, J. Kinne, H. Leonhardt, S. Magez, V. K. Nguyen, H. Revets, et al. 2009. Camelid immunoglobulins and nanobody technology. Vet. Immunol. Immunopathol. 128: 178-183.
3. Roovers, R. C., G. A. van Dongen, and P. M. van Bergen en Henegouwen. 2007. Nanobodies in therapeutic applications. Curr. Opin. Mol. Ther. 9: 327-335.
4. Wolfson, W. 2006. Ablynx makes nanobodies from llama bodies. Chem. Biol. 13: 1243-1244.
5. Schwede, T., A. Sali, B. Honig, M. Levitt, H. M. Berman, D. Jones, S. E. Brenner, S. K. Burley, R. Das, N. V. Dokholyan, et al. 2009. Outcome of a workshop on applications of protein models in biomedical research. Structure 17: 151-159.
6. Ablynx Corporate Overview. Available at: http://www.ablynx.com. Accessed: April 12, 2011.
7. De Genst, E., D. Saerens, S. Muyldermans, and K. Conrath. 2006. Antibody repertoire development in camelids. Dev. Comp. Immunol. 30: 187-198.
8. Verheesen, P., A. Roussis, H. J. de Haard, A. J. Groot, J. C. Stam, J. T. den Dunnen, R. R. Frants, A. J. Verkleij, C. Theo Verrips, and S. M. van der Maarel. 2006. Reliable and controllable antibody fragment selections from Camelid non-immune libraries for target validation. Biochim. Biophys. Acta 1764: 1307-1319.
9. Harmsen, M. M., and H. J. De Haard. 2007. Properties, production, and applications of camelid single-domain antibody fragments. Appl. Microbiol. Biotechnol. 77: 13-22.
10. Muyldermans, S., T. Atarhouch, J. Saldanha, J. A. Barbosa, and R. Hamers. 1994. Sequence and structure of VH domain from naturally occurring camel heavy chain immunoglobulins lacking light chains. Protein Eng. 7: 1129-1135. (Pubitemid 24282500)
11. Davies, J., and L. Riechmann. 1996. Single antibody domains as small recognition units: design and in vitro antigen selection of camelized, human VH domains with improved protein stability. Protein Eng. 9: 531-537. (Pubitemid 26261295)
12. Muyldermans, S., C. Cambillau, and L. Wyns. 2001. Recognition of antigens by single-domain antibody fragments: the superfluous luxury of paired domains. Trends Biochem. Sci. 26: 230-235.
13. Muyldermans, S., and M. Lauwereys. 1999. Unique single-domain antigen binding fragments derived from naturally occurring camel heavy-chain antibodies. J. Mol. Recognit. 12: 131-140.
14. Berman, H. M., J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, and P. E. Bourne. 2000. The Protein Data Bank. Nucleic Acids Res. 28: 235-242.
15. Sivasubramanian, A., A. Sircar, S. Chaudhury, and J. J. Gray. 2009. Toward high-resolution homology modeling of antibody Fv regions and application to antibody-antigen docking. Proteins 74: 497-514.
16. Jacobson, M. P., D. L. Pincus, C. S. Rapp, T. J. Day, B. Honig, D. E. Shaw, and R. A. Friesner. 2004. A hierarchical approach to all-atom protein loop prediction. Proteins 55: 351-367.
17. Mandell, D. J., E. A. Coutsias, and T. Kortemme. 2009. Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling. Nat. Methods 6: 551-552.
18. Marcatili, P., A. Rosi, and A. Tramontano. 2008. PIGS: automatic prediction of antibody structures. Bioinformatics 24: 1953-1954.
19. Chaudhury, S., and J. J. Gray. 2008. Conformer selection and induced fit in flexible backbone protein-protein docking using computational and NMR ensembles. J. Mol. Biol. 381: 1068-1087.
20. Sircar, A., and J. J. Gray. 2010. SnugDock: paratope structural optimization during antibody-antigen docking compensates for errors in antibody homology models. PLOS Comput. Biol. 6: e1000644.
21. Pearson, W. R., and D. J. Lipman. 1988. Improved tools for biological sequence comparison. Proc. Natl. Acad. Sci. USA 85: 2444-2448.
22. Edgar, R. C. 2004. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32: 1792-1797. (Pubitemid 38832724)
23. Galtier, N., M. Gouy, and C. Gautier. 1996. SEAVIEW and PHYLO-WIN: two graphic tools for sequence alignment and molecular phylogeny. Comput. Appl. Biosci. 12: 543-548.
24. DeLano, W. L. 2002. The PyMOL Molecular Graphics System. Available at: http://www.pymol.org. Accessed: April 12, 2011.
25. Altschul, S. F., W. Gish, W. Miller, E. W. Myers, and D. J. Lipman. 1990. Basic local alignment search tool. J. Mol. Biol. 215: 403-410.
26. Kuhlman, B., and D. Baker. 2000. Native protein sequences are close to optimal for their structures. Proc. Natl. Acad. Sci. USA 97: 10383-10388.
27. Sircar, A., E. T. Kim, and J. J. Gray. 2009. RosettaAntibody: antibody variable region homology modeling server. Nucleic Acids Res. 37(Web Server issue): W474-W479.
28. Rohl, C. A., C. E. Strauss, K. M. Misura, and D. Baker. 2004. Protein structure prediction using Rosetta. Methods Enzymol. 383: 66-93.
29. Canutescu, A. A., and R. L. Dunbrack, Jr. 2003. Cyclic coordinate descent: a robotics algorithm for protein loop closure. Protein Sci. 12: 963-972.
30. Wang, C., O. Schueler-Furman, and D. Baker. 2005. Improved side-chain modeling for protein-protein docking. Protein Sci. 14: 1328-1339.
31. Simons, K. T., C. Kooperberg, E. Huang, and D. Baker. 1997. Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions. J. Mol. Biol. 268: 209-225.
32. Al-Lazikani, B., A. M. Lesk, and C. Chothia. 1997. Standard conformations for the canonical structures of immunoglobulins. J. Mol. Biol. 273: 927-948.
33. Yin, S., F. Ding, and N. V. Dokholyan. 2007. Eris: an automated estimator of protein stability. Nat. Methods 4: 466-467.
34. Kabat, E. A., T. T. Wu, H. Bilofsky, M. Reid-Miller, and H. Perry. 1983. Sequence of Proteins of Immunological Interest. National Institutes of Health, Bethesda.
35. Abhinandan, K. R., and A. C. Martin. 2008. Analysis and improvements to Kabat and structurally correct numbering of antibody variable domains. Mol. Immunol. 45: 3832-3839.
36. Chothia, C., A. M. Lesk, E. Gherardi, I. M. Tomlinson, G. Walter, J. D. Marks, M. B. Llewelyn, and G. Winter. 1992. Structural repertoire of the human VH segments. J. Mol. Biol. 227: 799-817.
37. Wu, T. T., G. Johnson, and E. A. Kabat. 1993. Length distribution of CDRH3 in antibodies. Proteins 16: 1-7.
38. Shirai, H., A. Kidera, and H. Nakamura. 1996. Structural classification of CDRH3 in antibodies. FEBS Lett. 399: 1-8.
39. Conrath, K., C. Vincke, B. Stijlemans, J. Schymkowitz, K. Decanniere, L. Wyns, S. Muyldermans, and R. Loris. 2005. Antigen binding and solubility effects upon the veneering of a camel VHH in framework-2 to mimic a VH. J. Mol. Biol. 350: 112-125.
40. Spinelli, S., M. Tegoni, L. Frenken, C. van Vliet, and C. Cambillau. 2001. Lateral recognition of a dye hapten by a llama VHH domain. J. Mol. Biol. 311: 123-129.
41. De Genst, E., K. Silence, M. A. Ghahroudi, K. Decanniere, R. Loris, J. Kinne, L. Wyns, and S. Muyldermans. 2005. Strong in vivo maturation compensates for structurally restricted H3 loops in antibody repertoires. J. Biol. Chem. 280: 14114-14121.
42. Decanniere, K., S. Muyldermans, and L. Wyns. 2000. Canonical antigen-binding loop structures in immunoglobulins: more structures, more canonical classes? J. Mol. Biol. 300: 83-91.
43. Desmyter, A., S. Spinelli, F. Payan, M. Lauwereys, L. Wyns, S. Muyldermans, and C. Cambillau. 2002. Three camelid VHH domains in complex with porcine pancreatic α-amylase. Inhibition and versatility of binding topology. J. Biol. Chem. 277: 23645-23650.
44. Spinelli, S., A. Desmyter, C. T. Verrips, H. J. de Haard, S. Moineau, and C. Cambillau. 2006. Lactococcal bacteriophage p2 receptor-binding protein structure suggests a common ancestor gene with bacterial and mammalian viruses. Nat. Struct. Mol. Biol. 13: 85-89.
45. Bond, C. J., C. Wiesmann, J. C. Marsters, Jr., and S. S. Sidhu. 2005. A structure-based database of antibody variable domain diversity. J. Mol. Biol. 348: 699-709.
46. Capra, J. D., and J. M. Kehoe. 1974. Variable region sequences of five human immunoglobulin heavy chains of the VH3 subgroup: definitive identification of four heavy chain hypervariable regions. Proc. Natl. Acad. Sci. USA 71: 845-848.
47. Baca, M., L. G. Presta, S. J. O'Connor, and J. A. Wells. 1997. Antibody humanization using monovalent phage display. J. Biol. Chem. 272: 10678-10684.
48. Carter, P., L. Presta, C. M. Gorman, J. B. Ridgway, D. Henner, W. L. Wong, A. M. Rowland, C. Kotts, M. E. Carver, and H. M. Shepard. 1992. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Natl. Acad. Sci. USA 89: 4285-4289.
49. Spinelli, S., L. G. Frenken, P. Hermans, T. Verrips, K. Brown, M. Tegoni, and C. Cambillau. 2000. Camelid heavy-chain variable domains provide efficient combining sites to haptens. Biochemistry 39: 1217-1222. (Pubitemid 30090687)
50. Choi, Y., and C. M. Deane. 2010. FREAD revisited: accurate loop structure prediction using a database search algorithm. Proteins 78: 1431-1440.
51. Saerens, D., M. Pellis, R. Loris, E. Pardon, M. Dumoulin, A. Matagne, L. Wyns, S. Muyldermans, and K. Conrath. 2005. Identification of a universal VHH framework to graft non-canonical antigen-binding loops of camel single-domain antibodies. J. Mol. Biol. 352: 597-607.
52. Sellers, B. D., K. Zhu, S. Zhao, R. A. Friesner, and M. P. Jacobson. 2008. Toward better refinement of comparative models: predicting loops in inexact environments. Proteins 72: 959-971.
53. Danielson, M. L., and M. A. Lill. 2010. New computational method for prediction of interacting protein loop regions. Proteins 78: 1748-1759.
54. Lo Conte, L., C. Chothia, and J. Janin. 1999. The atomic structure of protein-protein recognition sites. J. Mol. Biol. 285: 2177-2198.
55. Fenwick, M. K., and F. A. Escobedo. 2003. Hybrid Monte Carlo with multidimensional replica exchanges: conformational equilibria of the hypervariable regions of a llama VHH antibody domain. Biopolymers 68: 160-177.
56. Fitch, C. A., S. T. Whitten, V. J. Hilser, and B. García-Moreno E. 2006. Molecular mechanisms of pH-driven conformational transitions of proteins: insights from continuum electrostatics calculations of acid unfolding. Proteins 63: 113-126.
57. Dimitrov, D. S. 2009. Engineered CH2 domains (nanoantibodies). MAbs 1: 26-28.
58. Sircar, A., S. Chaudhury, K. P. Kilambi, M. Berrondo, and J. J. Gray. 2010. A generalized approach to sampling backbone conformations with RosettaDock for CAPRI rounds 13-19. Proteins 78: 3115-3123.
59. Hwang, W. Y., J. C. Almagro, T. N. Buss, P. Tan, and J. Foote. 2005. Use of human germline genes in a CDR homology-based approach to antibody humanization. Methods 36: 35-42. (Pubitemid 40558814)
60. Humphris, E. L., and T. Kortemme. 2007. Design of multi-specificity in protein interfaces. PLOS Comput. Biol. 3: e164.
61. Karanicolas, J., and B. Kuhlman. 2009. Computational design of affinity and specificity at protein-protein interfaces. Curr. Opin. Struct. Biol. 19: 458-463.
62. Lippow, S. M., K. D. Wittrup, and B. Tidor. 2007. Computational design of antibody-affinity improvement beyond in vivo maturation. Nat. Biotechnol. 25: 1171-1176.
63. Pantazes, R. J., and C. D. Maranas. 2010. OptCDR: a general computational method for the design of antibody complementarity determining regions for targeted epitope binding. Protein Eng. Des. Sel. 23: 849-858.
64. Decanniere, K., T. R. Transue, A. Desmyter, D. Maes, S. Muyldermans, and L. Wyns. 2001. Degenerate interfaces in antigen-antibody complexes. J. Mol. Biol. 313: 473-478.
65. Stanfield, R., E. Cabezas, A. Satterthwait, E. Stura, A. Profy, and I. Wilson. 1999. Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing fabs. Structure 7: 131-142. (Pubitemid 29159699)
66. Decanniere, K., A. Desmyter, M. Lauwereys, M. A. Ghahroudi, S. Muyldermans, and L. Wyns. 1999. A single-domain antibody fragment in complex with RNase A: non-canonical loop structures and nanomolar affinity using two CDR loops. Structure 7: 361-370. (Pubitemid 29190470)